GENETIC VARIABILITY IN FORCED AND VOLUNTARY ENDURANCE EXERCISE PERFORMANCE IN SEVEN INBRED MOUSE STRAINS

Abstract

PURPOSE: The goal of this study was to characterize the genetic contribution to both forced and voluntary exercise performance and to determine whether performance in these two paradigms is controlled by similar genetic influences. METHODS: Seven inbred mouse strains (Balbc/ByJ, C3H/HeJ, C57BL/6J, DBA/1J, DBA/2J, FVB/NJ, and SW) were assessed for treadmill exercise performance and voluntary wheel performance. Expression of two molecular markers of cardiac hypertrophy (beta myosin heavy chain (β-MyHC) and atrial natriuretic factor (ANF)) was determined for all strains. Cardiac function was assessed via echocardiography and isolated work-performing heart preparations. RESULTS: There were marked strain differences in treadmill exercise performance, with SW and FVB/NJ mice showing elevated performance and C57BL/6J animals showing decreased performance compared to all other strains. Analysis of voluntary free-wheel performance also showed significant strain differences, with SW and C57BL/6J animals showing increased voluntary wheel activity compared to all other strains and DBA/1J animals showing decreased performance compared to all other strains. There was no correlation between treadmill performance and voluntary free-wheel performance. For treadmill and voluntary wheel performance, two estimates of heritability in the broad-sense, the intraclass correlation (rI) and the coefficient of genetic determination (g2) ranged from rI = 0.38 and g2 = 0.24 (average speed on the voluntary wheel) to rI = 0.90 and g2 = 0.82 (treadmill endurance test). DBA/1J and SW mice exhibited significantly greater cardiac contractility than all other analyzed strains while Balbc/ByJ mice exhibited significantly reduced cardiac contractility compared to all other strains. ANF and β-MyHC mRNA levels were significantly elevated in the DBA/2J myocardium compared to all other analyzed strains. CONCLUSIONS: The inbred mouse strains analyzed demonstrate markedly distinct endurance exercise capacities for both treadmill-based and voluntary wheel-based exercise paradigms. For the strains analyzed, treadmill performance did not predict voluntary wheel performance, and there was no correlation across strains between the relative performances for these two distinct exercise paradigms. There were significant strain differences for cardiac gene expression and cardiac function, but there was no significant correlation between any of these measures and either forced or voluntary exercise performance.